Advanced glycation endproducts and vascular AGEing.
Prof. dr. Casper Schalkwijk
Maastricht University Medical Centre,
Department of Internal Medicine,
P.O. Box 5800,
6202 AZ Maastricht,
The Netherlands.
[email protected].
The formation of advanced glycation endproducts (AGEs) is associated with the development of age-related diseases and is, at least in part, a likelymechanism accounting for vascular senescence.Protein glycation was viewed originally as a post-translational modification of proteins that accumulated slowly on long-lived proteins throughout life. In addition, glycation adducts are also formed in a fast manner on cellular and short-lived extracellular proteins and on DNA. The highly reactive methylglyoxal is a key compound involved in the very fast generation of glycation adducts on proteins, lipids and DNA. It has been demonstrated that the modification of proteins by methylglyoxal results in increased expression of adhesion molecules, growth factors and a sensitizing of cells to the effects pro-inflammatory cytokines. To counteract the deleterious effects of methylglyoxal, organisms contain glyoxalase I (GLO1), which concerts methylgyoxal to D-lactate.Several studies showed that there is a decline in the expression of GLO1 with age, which may contribute to increased risk of cardiovascular disease with ageing. Overexpression of the GLO1 gene (Glo1) not only counteracts the rise in methylglyoxal, AGEs and oxidative stress, but also prevents the development of endothelial dysfunction, and the microvascular complications. GLO1-transgenic aged rats showed amelioration of senescence.
In conclusion,GLO1belongs to the network of genes that influence longevity. The balance between the production of methylglyoxal and its detoxification by GLO1 can significantly contribute to the ageing process and to healthy ageing.
Prof. dr. Casper Schalkwijk
Maastricht University Medical Centre,
Department of Internal Medicine,
P.O. Box 5800,
6202 AZ Maastricht,
The Netherlands.
[email protected].
The formation of advanced glycation endproducts (AGEs) is associated with the development of age-related diseases and is, at least in part, a likelymechanism accounting for vascular senescence.Protein glycation was viewed originally as a post-translational modification of proteins that accumulated slowly on long-lived proteins throughout life. In addition, glycation adducts are also formed in a fast manner on cellular and short-lived extracellular proteins and on DNA. The highly reactive methylglyoxal is a key compound involved in the very fast generation of glycation adducts on proteins, lipids and DNA. It has been demonstrated that the modification of proteins by methylglyoxal results in increased expression of adhesion molecules, growth factors and a sensitizing of cells to the effects pro-inflammatory cytokines. To counteract the deleterious effects of methylglyoxal, organisms contain glyoxalase I (GLO1), which concerts methylgyoxal to D-lactate.Several studies showed that there is a decline in the expression of GLO1 with age, which may contribute to increased risk of cardiovascular disease with ageing. Overexpression of the GLO1 gene (Glo1) not only counteracts the rise in methylglyoxal, AGEs and oxidative stress, but also prevents the development of endothelial dysfunction, and the microvascular complications. GLO1-transgenic aged rats showed amelioration of senescence.
In conclusion,GLO1belongs to the network of genes that influence longevity. The balance between the production of methylglyoxal and its detoxification by GLO1 can significantly contribute to the ageing process and to healthy ageing.
